Background We have previously developed and confirmed a pragmatic molecular classifier for endometrial cancers; ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer). Inspired by the Cancer Genome Atlas, ProMisE identifies four prognostically distinct molecular subtypes and can be applied to diagnostic specimens (biopsy/curettings) enabling earlier informed decision-making. We have strictly adhered to the Institute of Medicine (IOM) guidelines for the development of genomic biomarkers, and herein present the final validation step of a locked-down classifier before clinical application. Patients and methods We assessed a retrospective cohort of women from the Tübingen University Women's Hospital treated for endometrial carcinoma between 2003 and 2013. Primary outcomes of overall, disease-specific, and progression-free survival were evaluated for clinical, pathological, and molecular features. Results Complete clinical and molecular data were evaluable from 452 women. Patient age ranged from 29 to 93 (median 65) years, and 87.8% cases were endometrioid histotype. Grade distribution included 282 (62.4%) G1, 75 (16.6%) G2, and 95 (21.0%) G3 tumors. 276 (61.1%) patients had stage IA disease, with the remaining stage IB [89 (19.7%)], stage II [26 (5.8%)], and stage III/IV [61 (13.5%)]. ProMisE molecular classification yielded 127 (28.1%) MMR-D, 42 (9.3%) POLE, 55 (12.2%) p53abn, and 228 (50.4%) p53wt. ProMisE was a prognostic marker for progression-free (P = 0.001) and disease-specific (P = 0.03) survival even after adjusting for known risk factors. Concordance between diagnostic and surgical specimens was highly favorable; accuracy 0.91, κ 0.88. Discussion We have developed, confirmed, and now validated a pragmatic molecular classification tool (ProMisE) that provides consistent categorization of tumors and identifies four distinct prognostic molecular subtypes. ProMisE can be applied to diagnostic samples and thus could be used to inform surgical procedure(s) and/or need for adjuvant therapy. Based on the IOM guidelines this classifier is now ready for clinical evaluation through prospective clinical trials.

中文翻译：

---

ProMisE分子分类器在大量基于人群的病例系列中对子宫内膜癌的最终验证。

背景我们之前已经开发并证实了一种实用的子宫内膜癌分子分类器。ProMisE（子宫内膜癌的主动分子风险分类器）。受癌症基因组图谱的启发，ProMisE可以识别出四种在预后上不同的分子亚型，并可以应用于诊断标本（活组织检查/刮除术），从而能够更早地做出明智的决策。我们严格遵守医学研究所（IOM）的基因组生物标志物开发指南，在此介绍了临床应用之前锁定分类器的最终验证步骤。患者和方法我们评估了蒂宾根大学妇女医院2003年至2013年间接受过子宫内膜癌治疗的妇女的回顾性队列研究。评估无进展生存期和无进展生存期的临床，病理和分子特征。结果从452名女性中评估了完整的临床和分子数据。患者年龄为29岁至93岁（中位数65岁），子宫内膜样组织型为87.8％。等级分布包括282个（62.4％）G1、75个（16.6％）G2和95个（21.0％）G3肿瘤。276名（61.1％）患者患有IA期疾病，其余的IB期[89（19.7％）]，II期[26（5.8％）]和III / IV期[61（13.5％）]。ProMisE分子分类产生127（28.1％）MMR-D，42（9.3％）POLE，55（12.2％）p53abn和228（50.4％）p53wt。ProMisE是无进展（P = 0.001）和疾病特异性（P = 0.03）生存的预后标志物，即使在调整了已知的危险因素后也是如此。诊断和手术标本之间的一致性非常好。精度0.91，κ0。88.讨论我们已经开发，确认并验证了一种实用的分子分类工具（ProMisE），该工具可对肿瘤进行一致的分类并确定四种不同的预后分子亚型。ProMisE可以应用于诊断样本，因此可以用于告知手术程序和/或需要辅助治疗。根据IOM指南，该分类器现已准备就绪，可以通过前瞻性临床试验进行临床评估。